Hyperphosphatemia is a pathologic condition due to different diseases, for example inadequate renal function, renal disease, kidney failure, in particular patients undergoing dialysis; hypoparatiroidism; osteoporosis, atherosclerosis. For a review of this problem, see U.S. Pat. No. 5,496,545 and references cited therein.
Cardiovascular alterations due to calcification of vessels, myocardium and heart valves represent the major mortality and morbidity cause in uremic patients (Burke, S. K., Seminars in Nephrology, vol. 24, no 5, 403-407, 2004; Levin, N V, et al.; Seminars in Nephrology, vol. 42, no 55, 396-400, 2004).
Most of patients undergoing dialysis or affected by chronic renal failure in conservative treatment show increased phosphorus serum levels, which are responsible of calcifications in tissues other than bone tissue and which are responsible of increased risk of cardiovascular mortality (Moe, S M, Seminars in Nephrology, vol. 24, no 5, 413-416, 2004; Eknoyan, G., et al.; Am. Kidney Dis., 42, 4, 1-204, October 2003).
Phosphorus intake occurs with food and it is very difficult to avoid it. For example, patients undergoing dialysis must eat meat, a food rich in phosphorus. On the other hand, low-protein food has a low amount of phosphorus, but its use can determine malnutrition.
It was demonstrated by scientific evidence that prevention and/or early treatment of hyperphosphoremia in uremic patients can reduce morbidity and mortality risk. Moreover, increased phosphorus serum level can stimulate higher calcium deposition in cells and bone tissue protein and enzyme synthesis and increased risk of vessel calcification (Burke, ibid.).
Accordingly, controlling phosphorus serum levels is a necessary action for reducing cardiovascular morbidity and mortality in this kind of patients, but also can be a general health prevention in population, particularly exposed to risk of cardiovascular disease.
To date, high phosphorus serum levels are treated with vitamin D or substances, which, when administered by oral route, bind phosphorus through chelating action (phosphorus binders) and eliminate it by fecal route. Although effective in their action of eliminating phosphorus, some of these substances must be avoided because of their side effects, which, in some cases can be quite severe. For example, substances containing calcium, magnesium or aluminium are avoided by those expert in the field. Lanthanum is an effective absorbing substance but its toxicity is a hamper to its use in this field.
The current treatments are focused on absorbing phosphorus from food, the main source of it, by administering suitable drugs in concomitance with meals.
The leading therapy is represented by non-absorbed, calcium and metal-free phosphorus binders. A successfully marketed drug is Sevelamer (Renagel®), based on a polyallylamine, see U.S. Pat. Nos. 5,496,545, U.S. Pat. No. 5,667,775, U.S. Pat. No. 6,756,363 and U.S. Pat. No. 6,562,329.
Current therapy is used only to limit dietary phosphorus intake by binding phosphorus content in food, but is ineffective of phosphorus serum levels and cellular content.
The problem of an improved treatment of high phosphorus levels is still strongly felt by those skilled in the art, especially in view of the importance of such a treatment with respect to patients affected by renal diseases, in particular uremic patients undergoing dialysis.
The inventor discovered that, in the fasting interval, considerable amounts of phosphorus are secreted in saliva, which is continuously ingested and gastric secretions, so partly nullifying the therapeutic or preventive action of the drugs taken at the meals.
By this phenomenon, phosphorus is recirculated in the body and contributes to maintain high serum levels, thus making difficult to achieve an effective management of the risk of cardiovascular diseases, especially in those patients particularly exposed to said risk, such as patients affected by kidney failure and/or undergoing periodical dialysis.